Resistance to the safest and most commonly used pediculicides in the U.S. and globally are giving rise to head louse epidemics and increasing number of serious side effects resulting from multiple treatments/failures and frustrated people resorting to more hazardous alternatives. There exists a pressing need for information concerning head louse biology, toxicology and population genetics, particularly those factors controlling transmission, extent of pyrethroid and malathion resistance, and how best to monitor for resistance and optimize treatments. There is detailed information on the resistance mechanisms for the pyrethrins/pyrethroids and malathion in many pest insects that will allow us to rapidly and efficiently obtain a complete database for head lice and use it to make effective control decisions. The kdr resistance factor is identified and we can monitor it efficiently and affordably at the genotypic level to judge the effectiveness of our control choices. Recent published biochemical results have determined that malathion carboxylesterase is a major resistance mechanism. Our in situ bioassay allows us to apply pediculicides and to monitor their effectiveness in a controlled and reproducible manner (semi-clinical) that largely simulates the human head at a fraction of the cost of clinical studies so that only those strategies that have a high level of success are taken to clinical studies. In response to these published and in press results, the specific aims of this resubmitted application are: 1). Knockdown resistance (kdr): A model to develop tools for management; 2). Molecular biology underlying malathion resistance due to the hydrolytic esterases. [unreadable] [unreadable] [unreadable]